BioMed Research International

BioMed Research International / 2014 / Article

Review Article | Open Access

Volume 2014 |Article ID 480258 |

Shamala Salvamani, Baskaran Gunasekaran, Noor Azmi Shaharuddin, Siti Aqlima Ahmad, Mohd Yunus Shukor, "Antiartherosclerotic Effects of Plant Flavonoids", BioMed Research International, vol. 2014, Article ID 480258, 11 pages, 2014.

Antiartherosclerotic Effects of Plant Flavonoids

Academic Editor: Senthil K. Venugopal
Received13 Nov 2013
Revised11 May 2014
Accepted11 May 2014
Published27 May 2014


Atherosclerosis is the process of hardening and narrowing the arteries. Atherosclerosis is generally associated with cardiovascular diseases such as strokes, heart attacks, and peripheral vascular diseases. Since the usage of the synthetic drug, statins, leads to various side effects, the plants flavonoids with antiartherosclerotic activity gained much attention and were proven to reduce the risk of atherosclerosis in vitro and in vivo based on different animal models. The flavonoids compounds also exhibit lipid lowering effects and anti-inflammatory and antiatherogenic properties. The future development of flavonoids-based drugs is believed to provide significant effects on atherosclerosis and its related diseases. This paper discusses the antiatherosclerotic effects of selected plant flavonoids such as quercetin, kaempferol, myricetin, rutin, naringenin, catechin, fisetin, and gossypetin.

1. Introduction

Being a chronic inflammatory disease, atherosclerosis is becoming the leading cause of death in most of the developed countries [1]. Cardiovascular diseases (CVDs) like myocardial infarction (heart attack), acute coronary syndrome, or stroke arise through the development of plaques and lesions inside the arteries [25]. Hypercholesterolemia, hypertension, and obesity give high risks for the progression of CVDs. Statins are widely used as the clinical treatment for atherosclerosis due to its excellent efficacy in reducing the low density lipoprotein (LDL) level [6, 7]. Statins competitively inhibit the HMG-CoA reductase enzyme that plays a great role in catalyzing the rate-limiting step in the biosynthesis of cholesterol [8]. The increase in hepatic LDL receptors’ expression is triggered by the reduction of hepatocyte cholesterol concentration and helps to clear LDL from the circulation [9, 10].

However, the consumption of statins causes adverse health effects such as liver injury and muscle toxicity [10, 11]. The other side effects include myopathy, rhabdomyolysis, and acute renal failure [12]. Thus, attention is now directed to the natural products from plant origin that possess antiartherosclerotic activity and can promote human health. This can eventually avoid possible health effects due to the long period consumption of statins. Many researches on bioactive compounds and their possible medicinal attributes have been studied during the past decades [1315]. Plant and plant by-products can be used for isolating health-promoting bioactive compounds since there are substantial plant sources which are relatively inexpensive. The bioactive compound from plant extracts has shown plentiful health-promoting effects in both in vitro and in vivo studies, such as antioxidant [16, 17], hypoglycemic [1820], hypotensive [21], and hypocholesterolemic [2224] effects. The aim of this review is to provide the reader with some important evidence on the antiatherosclerotic activity of selected flavonoids that are mostly found in plants.

2. Flavonoids

Flavonoids represent a broad family of more than 4000 secondary plant metabolites. The four predominant classes are 4-oxoflavonoids (flavones and flavonols), isoflavones, anthocyanins, and flavan-3-ol derivatives (tannins and catechin) [2527]. For centuries, preparations that contain flavonoids are applied as the primary physiologically active components that have been used for treating human diseases [28]. Epidemiological studies have shown that the risk of heart diseases can be reduced through the consumption of flavonoid-rich diets [29]. Flavonoids may inhibit the vascular diseases’ development through alteration in endothelial cell eicosanoid production [30]. Flavonoids also showed blood pressure lowering effect in hypertensive and normotensive subjects while flavonoids may have beneficial actions in obesity due to their capacity to regulate fatty oxidation and improve adipocyte functionality [31]. Besides, food derived flavonols (quercetin, kaempferol, and myricetin) have been reported to exhibit various biological functions and medicinal properties such as antioxidant, antithrombotic, anti-inflammatory, anti atherogenic, antiatherosclerotic, and cardioprotective effects [3235]. The plants like Garcinia cambogia [36], Mangifera indica [37], Hypericum perforatum L [38], and Asparagus racemosus [39] that contain flavonoids have been proven to significantly lower the risk of atherosclerosis and CVD.

2.1. Quercetin

Flavonoids such as quercetin (3′,4′,3,5,7-pentahydroxyflavone) have gained considerable attention mainly due to their broad spectrum of health beneficial effects for the treatment of CVDs. Quercetin has been reported to improve endothelium-dependent vasorelaxation in aorta, decreases systolic blood pressure, and reduces cardiac hypertrophy and proteinuria in hypertensive rats [40, 41]. Sánchez et al. [42] reported that enhancement of endothelial nitric oxide synthase (eNOS) activity and reduction of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated superoxide production with downregulation of expression showed the antihypertensive effects of quercetin. Besides that, quercetin has been proven to improve dyslipidemia, decrease oxidative stress through stimulation of lipolysis activity, and upregulate the adipocytes genes expression which increases the lipids beta oxidation [43, 44]. Quercetin treatment in obesity animal models showed reduction in body weight, visceral and subcutaneous adipose tissue, and liver fat accumulation. Moreover, quercetin also suppressed the peroxisome proliferator-activated receptor y (PPARy) and sterol regulatory element-binding proteins (SREBP) expression. The reduction in the expression of PPARy indicates reduction in adipogenesis [4547]. On the other hand, Morus alba L leaves containing quercetin 3-(6-malonylglucoside) (Q3MG) as their major flavonol attenuated the development of artherosclerotic lesion in LDL receptor-deficient mice through LDL resistance enhancement to oxidative modification and the artherosclerotic lesion in M. alba-treated mice was significantly reduced by 52% [48]. Kleemann et al. [35] reported on the anti-inflammatory and antiatherogenic effects of the quercetin and have shown that short-term treatment for 14 days with dietary quercetin managed to completely quench the cytokine-induced expression of human C-reactive protein (CRP) in transgenic mice. The elevating level of CRP is an inflammation marker that increases the risk of CVDs [35, 49]. Bhaskar et al. [50] investigated the antiatherosclerotic property of quercetin and found notable regression of atherosclerosis in the histopathological examination of the aorta in hypercholesterolemic rabbits supplemented with quercetin. This suggests the potential of quercetin as an alternative therapeutic agent for atherosclerosis and CVDs as well as for hypertension and obesity that can lead to CVDs [5052]. Camellia chinensis [53, 54], Allium fistulosum and Calamus scipionum [54], Moringa oleifera [17, 55], Centella asiatica [56], Hypericum hircinum [57], and Hypericum perforatum [58] have been reported to have high content of quercetin.

2.2. Kaempferol

Numerous researches have been conducted on kaempferol (3,4′,5,7-tetrahydroxyflavone) and studies have shown that consumption of kaempferol-rich foods reduced the risk of developing cardiovascular diseases [59, 60]. Kaempferol has been reported to increase endothelium relaxation in coronary artery of porcine [61]. Xiao et al. [62] investigated kaempferol’s protective effects against endothelial damage and found that kaempferol improves the nitric acid production and reduces asymmetric dimethylarginine level which enhances the endothelium-dependent vasorelaxation, preventing endothelium injuries and oxidative damage in cells. The ability of kaempferol in reducing oxidative stress can be the beneficial effect in CDVs [63]. Kaempferol also prevents arteriosclerosis by the inhibition of LDL oxidation and formation of platelets. Kowalski et al. [64] demonstrated that the monocyte chemoattractant protein (MCP-1) is inhibited by kaempferol in an in vitro study. MCP-1 involves in the initial stage of plaque formation in arteriosclerosis. Kong et al. [65] evaluated the effect of kaempferol on atherosclerosis induced rabbit models, and upon 10-week treatment of kaempferol with high cholesterol diet, the expression of intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and MCP-1 in the rabbits’ aorta has been significantly downregulated. This indicates that kaempferol can alleviate vascular inflammation to prevent atherosclerosis. Moringa oleifera constitutes kaempferol as one of its major bioactive compound [17, 55] which was proven to possess antiatherosclerotic and hypolipidemic properties and has therapeutic potential in the treatment of hyperlipidemia, atherosclerosis, and cardiovascular diseases [66, 67]. Therefore, kaempferol can be considered to be an effective and potent agent against atherosclerosis. The presence of kaempferol has been identified in many other plants and some of them are Centella asiatica [56], Euonymus alatus [68], Kaempferia galanga L [69], Ginkgo biloba, Equisetum spp., Tilia spp., Sophora japonica, and propolis [60].

2.3. Myricetin

Myricetin (3,3′,4′,5,5′,7-hexahydroxyflavone) is a natural flavonol found in vegetables, fruits, berries, tea, and medicinal plants [70]. Various health related studies on myricetin from plant sources have been demonstrated which revealed the antioxidant, antiviral, anticarcinogenic, antiplatelet, hypoglycemic, and cytoprotective properties of myricetin [59, 7176]. Myricetin also possesses antihypertensive action. Godse et al. [77] reported that myricetin prevent the progression of high blood pressure and reversed the metabolic alterations in fructose-induced rats. Besides, myricetin was proven to suppress body weight gain and fat accumulation by increasing oxidation of fatty acids which is due to upregulation of hepatic peroxisome proliferator activated receptor (PPARα) and downregulation of hepatic sterol regulatory element-binding proteins (SREBPs) expressions in high fat-induced rats. These results revealed the antiobesity and antihyperlipidemic effects of myricetin [78]. Myricetin also was proven to possess protective effects on the oxidation of LDL in blood [79, 80]. Ha et al. [79] reported that Ampelopsis cantoniensis has myricetin as its main constituent and managed to inhibit the LDL oxidation induced by metal ion (Cu2+) and free radical (AAPH), and therefore the A. cantoniensis extract can be utilized as a natural remedy to prevent the oxidation of LDL which is involved in the formation atherosclerotic lesion. Lian et al. [80] revealed that besides preventing the LDL from oxidation, myricetin also blocks the oxidized LDL uptake by macrophages and plays an essential role in preventing atherosclerosis. In vivo studies on antiartherosclerotic effects of myricetin could further provide better knowledge and understanding of its role in ameliorating atherosclerosis. High content of myricetin has been also reported in these plants: Myrica cerifera L [81], Calamus scipionum [54], Chrysobalanus icaco L [82], Moringa oleifera, and Aloe vera [17].

2.4. Rutin

Rutin (quercetin-3-rutinoside) is a bioflavonoid commonly found in buckwheat bran, black tea, and citrus fruits [83]. Rutin contributes to many positive health effects such as powerful antioxidant [84], protects against free radicals [85], possess anti-inflammatory properties [86, 87], and suppresses aldose reductase activity [88]. Endothelial dysfunction plays a major role in the development of CDVs and it is found in conditions such as hypertension, hypercholesterolemia, and atherosclerosis. Rutin in buckwheat extract decreases body weight, improves capillary fragility to maintain blood pressure, and significantly reduced nitrotyrosine immunoreactivity in endothelial cells of aorta [89]. Rutin has been proven to exhibit antiobesity effect via suppression of oxidative stress, dyslipidemia, and hepatosteatosis in obese rats. Rutin decreases liver and adipose tissue weight, suppresses hepatic triacylglycerol and cholesterol level, and enhances antioxidant enzymes (superoxide dismutase and glutathione peroxidase) activities in obese rats [90]. On the other hand, rutin plays a great role in preventing atherosclerosis and the evidence for its antiatherosclerotic effects is available in in vivo studies: rabbits [91], rat [92], and hamsters [93]. Voskresensky and Bobyrev [91] showed that rutin delays the hypercholesterolemia development and inhibits the atherosclerotic formation in rabbits’ aorta. While, Santos et al. [92] researched into the effects of rutin on controlling lipid metabolism and found that rutin reduced the cholesterol levels and has the lowest level of triacylglycerol in hypercholesterolemia rats. In addition, rutin extracted from Dimorphandra mollis showed decreases in the level of plasma triglyceride of hypercholesterolemia induced hamsters without changing the high-density lipoprotein (HDL) cholesterol and total cholesterol levels. Rutin was also proven to be nontoxic and no notable changes were observed in total white bloods cells and mononuclear and granulocytes cells compared to the untreated control group [93]. Therefore, rutin can be developed as an alternative drug for the treatment of atherosclerosis. Other plants that constitute rutin compound are Flos hippocastani [94], Ruta graveolens [95], Rhus cotinus [96], and Phyllanthus amarus [97].

2.5. Naringenin

Naringenin (4′,5,7-trihydroxyflavanone) has been widely studied in issues related to atherosclerosis. Naringenin was reported to have poor antioxidant properties compared to other flavanoids but it is still able to be a potential inhibitor in cholesterol biosynthesis [98, 99]. Borradaile et al. [100] claimed that naringenin regulates apolipoprotein B secretion by HepG2 cells directly through inhibition of cholesterol ester synthesis. Naringenin also reported to affect lipid metabolism through inhibition of acyl coenzyme A: cholesterol O-acyltransferase and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase in rats [101, 102]. Study on higher animal models, rabbits, was conducted by Kurowska et al. [103] whereby the results obtained showed decrease in hepatic cholesterol and LDL levels. Meanwhile, studies performed on hypercholesterolemic human subjects showed increase in HDL levels after consumption of naringenin rich orange juices [104]. Lee et al. [105] demonstrated that (2S)-naringenin, isolated from Typha angustata, inhibits the vascular smooth muscle cells (VSMCs) proliferation while Mulvihill et al. [106] reported that naringenin-treated mice showed about 60% reduction of aortic cholesterol and decreases the level of hepatic cholesteryl ester, very low-density lipoprotein (VLDL) and low density lipoprotein (LDL). These lead to the reduction in cholesterol and triglyceride accumulation within the arterial wall and ameliorates atherosclerosis. Besides, naringenin also prevents accumulation of adipose, adipocyte hypertrophy, and dyslipidemia [106]. Other biological activities of naringenin include anti-inflammatory, anticancer, and positive effects on sex metabolism through binding to estrogen receptors [107112]. Naringenin is a potential flavonoid to be explored further especially in atherosclerosis since it has numerous health benefits. Some of the plant sources that are rich in naringenin are Solanum lycopersicum and citrus fruits [113, 114], Mentha aquatica L [115], immature fruit of Citrus aurantium [116], and flowers of Acacia podalyriifolia [117].

2.6. Catechin

Catechin [(2R,3S)-3′,4′,5,7-tetrahydroxyflavan-3-ol] has been reported to effectively inhibit lipid peroxidation and scavenge free radicals [118, 119]. Catechin is known to possess preventive effect in CVDs due to its involvement in oxidative process in atherogenesis [120]. Being antioxidant, catechin is able to modulate cellular signaling pathways that lead to elevation of vascular reactivity, platelet aggregation, and reduction of inflammation [121124]. Diverse studies have been conducted using tea (Camellia sinensis) which contains catechin believed to play a major role as cardioprotective plant source [123]. Almost 50–80% of the total catechin from tea is epigallocatechin-3-gallate (EGCG) and it is considered to be the most effective bioactive component in cholesterol lowering [125]. Proinflammatory cytokine and tumor necrosis factor-alpha (TNFα) commonly exist in atherosclerotic lesions which have direct effect on monocyte chemotactic protein-1 (MCP-1) stimulation and vascular endothelial cells. MCP-1 plays an important role in the monocytes’ recruitment in developing inflammatory CDVs. EGCG inhibits TNFα activation and resulted in reduction of MCP-1 production in coronary vascular endothelial cell [126]. Furuyashiki et al. [127] demonstrated that EGCG at low concentration (5 μM) is able to suppress intracellular lipid accumulation in an in vitro model suggesting that the cholesterol lowering effect of EGCG is due to the influence on intestinal lipid absorption. Clinical studies done by Potenza et al. [128] in hypertensive rats suggested that EGCG was shown to reduce blood pressure, raise adiponectin levels, protect against myocardial injury, and improve endothelial function which was proven to reduce the CVDs risk. Another study done by Bursill and Roach [129] confirmed that EGCG lowers the cholesterol and triglyceride absorption in rats. Studies conducted on humans by Widlansky et al. [130] claim that EGCG can reverse endothelial dysfunction and improve dilation of brachial artery in patients with coronary artery disease. These studies suggest the efficiency of EGCG as a potential agent for treating CVD. Other plant sources that are rich in catechins are Betula pubescens and Betula pendula [131], Cocos nucifera [132], fruit pulp of Argania spinosa [133], and Cassia fistula [134].

2.7. Fisetin

Fisetin (3,7,3′,4′-tetrahydroxyflavone) together with morin and myricetin is structural related flavan-3-ol and is commonly distributed in vegetables and fruits such as apple, strawberry, grape, persimmon, cucumber, and onion at concentrations of 2–160 μg/g [135]. Fisetin is known for its strong antioxidative [136], anti-inflammatory [137], anticancer [138], antiproliferative [139], and antihyperglycemic [140] activities. Increase in adipocyte cell number (hyperplasia) is an essential therapeutic target for the prevention of obesity [141]. Jung et al. [142] demonstrated that fisetin ameliorates diet-induced obesity by inhibition of mammalian target of rapamycin complex I (mTORCI) signalling which is central mediator for lipid biosynthesis, cellular growth, and proliferation. Fisetin supplementation in high-fat diet-induced mice regulated fat accumulation in adipose tissue and suppresses adipogenesis during the adipocyte differentiation via downregulation of related gene and thus the study proves that fisetin can be an effective antiobesity agent [142]. The development of atherosclerotic lesion is induced by the elevated concentrations of LDL, blood cholesterol, and triglycerides [143]. Macrophages play an essential role in the development of atherosclerosis by accumulating cholesterol in foam cells [144]. Fisetin inhibits LDL oxidation by macrophages and plays a role as free radical scavenger in LDL which also inhibits the oxidative enzymes from macrophage [145]. Thiobarbituric acid-reactive substances assay (TBARS), electrophoretic mobility, and conjugated diene formation analyses by Lian et al. [80] have shown that fisetin inhibits Cu2+ mediated LDL oxidation stronger than morin and myricetin. Binding of CD36 (class B scavenger receptor) to oxidized LDL causes the formation of atherosclerotic lesion. Fisetin blocks macrophage’s oxidized LDL uptake by reducing the CD36 expression on the macrophages [80]. However, the study of fisetin in vivo atherosclerosis models is still lacking. The participation of fisetin in ameliorating atherosclerosis can further be confirmed in animal model studies for future flavonoids-based drugs. Plants like Butea frondosa, Gleditsia triacanthos, Quebracho colorado [146], Curcuma longa [147], Rhus verniciflua [148], Acacia greggii, and Acacia berlandieri [149] are rich sources of fisetin.

2.8. Gossypetin

Gossypetin (3,5,7,8,3′,4′-hexahydroxyflavone) was originally isolated from Hibiscus spp. [151]. Gossypetin suppressed the oxidation of LDL [143] and was able to modify the LDL in a form accepted by macrophage through elevated affinity process in a nonoxidative mechanism [154]. Lin et al. [150] reported that gossypetin is an important flavonoid from Hibiscus sabdariffa and has been shown to prevent atherosclerosis, reduce oxidative stress, and neutralize agents that cause cancer. H. Sabdariffa extract revealed the potential of gossypetin in inhibiting atherosclerosis in hyperlipidemic rabbits [150]. Chen et al. [151] published the first report on the antiatherosclerotic activity of gossypetin in in vitro study and demonstrated that gossypetin inhibits both lipoprotein oxidation and lipid peroxidation. Gossypetin functions against oxidative LDL and accumulation of intracellular lipid through the regulation of peroxisome proliferator-activated receptor (PPAR) signals which stimulated the cholesterol to be removed from macrophages and retard the atherosclerosis process [151]. The findings mentioned strongly suggest the development of gossypetin as an antiatherosclerotic agent. H. Sabdariffa extract has been used as antihypertensive agent since it decreases systolic blood and pulse pressure [155]. Villalpando-Arteaga et al. [156] reported that H. Sabdariffa aqueous extract possesses antilipidemic, antiobesity, and hepatoprotective effects. Studies on the role of gossypetin against hypertension and obesity can further reveal its beneficial effects and pharmacological activities. Besides H. Sabdariffa, gossypetin also is present in H. vitifolius, H. esculentus, Empetrum nigrum and Acacia constricta [152], H. rosa-sinensis, Chiranthodendron pentadactylon, Fremontia californica, Thespesia populnea, and Fagonia cretica [153].

3. Conclusion

The summary of reported plant flavonoids is shown in Table 1. Various flavonoids compounds that are available in plants exhibit numerous effects that can prevent the progression of atherosclerosis and diseases such as hypercholesterolemia, hypertension, and obesity that can lead to CVDs. In vivo studies on myricetin and fisetin could give better view on its potential as an antiatherosclerotic agent. Investigation of potential effects of gossypetin against hypertension and obesity is suggested. Future research can be focused on the role of plant flavonoids in human metabolism and signaling pathway involved during the therapy of atherosclerosis. This could help to determine the strategies of improving the alternatives therapeutic approaches for atherosclerosis and other related diseases. Since there is an urge for alternatives natural treatment due to the side effects of statins, flavonoid-based drugs can be utilized for the prevention and treatment of atherosclerosis and CVDs.


QuercetinAnti-inflammatory [35] 
Antihypertensive [40] 
Vasodilator effects [41] 
Antiobesity [47]
Antihypercholesterolemic and antiatherosclerotic [50]
Morus  alba  L [48]
Camellia  chinensis [53, 54]
Allium  fistulosum  and  Calamus scipionum[54]
Moringa  oleifera [17, 55]
Centella  asiatica [56]
Hypericum  hircinum [57]
Hypericum  perforatum [58]

KaempferolEnhances endothelium vasorelaxation [61] 
Protective effects against endothelial damage [62] 
Reduce oxidative stress [63] 
Antiatherosclerotic [65] 
Antihyperlipidemic [67]
Moringa  oleifera [17, 55]
Centella  asiatica [56]
Ginkgo  biloba,  Equisetum  spp.,  Tilia spp.,  Sophora  japonica, and propolis [60]
Euonymus  alatus [68]
Kaempferia  galanga L [69]

MyricetinAntiplatelet [75]
Cytoprotective effects [76]
Antihypertensive [77]
Antiobesity and antihyperlipidemic [78]
Antiartherosclerotic [80]
Calamus  scipronum [54]
Moringa  oleifera and Aloe  vera [17]
Ampelopsis  cantoniensis [79]
Myrica cerifera L [81]
Chrysobalanus  icaco L [82]

RutinAnti-inflammatory [86, 87] 
Improves capillary fragility and antihypertensive [89] 
Suppresses oxidative stress and antiobesity [90] 
Antiartherosclerotic [91] 
Antihypercholesterolemic [93]
Dimorphandra  mollis [93]
Flos  hippocastani [94]
Ruta  graveolens [95]
Rhus  cotinus [96]
Phyllanthus  amarus [97]

NaringeninAntihypercholesterolemic [104]
Antiatherogenic and antiobesity [106]
Anti-inflammatory [111]
Typha  angustata [105]
Solanum  lycopersicum and citrus  fruits [113, 114]
Mentha  aquatica L [115]
Citrus  aurantium [116]
Acacia  podalyriifolia [117]

CatechinAntiplatelet and anti-inflammatory [121124]
Cardioprotective effects [123]
Antiatherosclerotic [126]
Antihypercholesterolemic [127]
Antihypertensive [128]
Camellia  sinensis [123, 125130]
Betula  pubescens  and  Betula  pendula [131]
Cocos  nucifera [132]
Argania  spinosa [133]
Cassia  fistula [134]

FisetinAntioxidative [136]
Anti-inflammatory [137]
Antiproliferative [139]
Antiobesity [142]
Antiatherosclerotic [80]
Butea  frondosa,  Gleditsia  triacanthos,  and  Quebracho  colorado [146]
Curcuma  longa [147]
Rhus  verniciflua [148]
Acacia  greggii and Acacia  berlandieri [149]

GossypetinSuppresses LDL oxidation [143] 
Reduces oxidative stress [150] 
Antihyperlipidemic [150] 
Antiatherosclerotic [151]
Hibiscus  spp. [151]
Hibiscus  sabdariffa [150]
Hibiscus  vitifolius,  Hibiscus esculentus,  Empetrum  nigrum, and Acacia  constricta [152]
Hibiscus  rosa-sinensis,  Chiranthodendron  pentadactylon,   Fremontia  californica,  Thespesia  populnea,  and  Fagonia  cretica [153]


The authors declare that the original paper has not been previously published and that it is not being considered elsewhere for publication and that, if accepted, it will not be published in all forms and media, without the consent of the editor and publisher. All authors agree to submit the paper and agree that the corresponding author acts on their behalf throughout the review and publication process.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

Authors’ Contribution

Shamala Salvamani and Baskaran Gunasekaran contributed equally to this work.


  1. C. Margaret, “Burden: mortality, morbidity and risk factors,” Global Status Report on Non Communicable Diseases, 2010. View at: Google Scholar
  2. M. Navab, J. A. Berliner, A. D. Watson et al., “The Yin and Yang of oxidation in the development of the fatty streak,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 16, no. 7, pp. 831–842, 1996. View at: Google Scholar
  3. R. Ross, “Atherosclerosis—an inflammatory disease,” The New England Journal of Medicine, vol. 340, no. 2, pp. 115–126, 1999. View at: Publisher Site | Google Scholar
  4. D. Steinberg and J. L. Witztum, Lipoproteins, Lipoprotein, Oxidation, and Atherogenesis, WB Saunders, Philadelphia, Pa, USA, 1999.
  5. J. F. Keaney Jr., “Atherosclerosis: from lesion formation to plaque activation and endothelial dysfunction,” Molecular Aspects of Medicine, vol. 21, no. 4-5, pp. 99–166, 2000. View at: Publisher Site | Google Scholar
  6. A. L. Gould, J. E. Rossouw, N. C. Santanello, J. F. Heyse, and C. D. Furberg, “Cholesterol reduction yields clinical benefit: impact of statin trials,” Circulation, vol. 97, no. 10, pp. 946–952, 1998. View at: Google Scholar
  7. K. K. Ray and C. P. Cannon, “The potential relevance of the multiple lipid-independent (Pleiotropic) effects of statins in the management of acute coronary syndromes,” Journal of the American College of Cardiology, vol. 46, no. 8, pp. 1425–1433, 2005. View at: Publisher Site | Google Scholar
  8. A. Endo, Y. Tsujita, M. Kuroda, and K. Tanzawa, “Inhibition of cholesterol synthesis in vitro and in vivo by ML 236A and ML 236B, competitive inhibitors of 3 hydroxy 3 methylglutaryl Coenzyme A reductase,” European Journal of Biochemistry, vol. 77, no. 1, pp. 31–36, 1977. View at: Google Scholar
  9. M. S. Brown and J. L. Goldstein, “A receptor-mediated pathway for cholesterol homeostasis,” Science, vol. 232, no. 4746, pp. 34–47, 1986. View at: Google Scholar
  10. D. J. Maron, G. P. Lu, N. S. Cai et al., “Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial,” Archives of Internal Medicine, vol. 163, no. 12, pp. 1448–1453, 2003. View at: Publisher Site | Google Scholar
  11. R. H. Bradford, C. L. Shear, A. N. Chremos et al., “Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia,” Archives of Internal Medicine, vol. 151, no. 1, pp. 43–49, 1991. View at: Publisher Site | Google Scholar
  12. L. R. Pierce, D. K. Wysowski, and T. P. Gross, “Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy,” Journal of the American Medical Association, vol. 264, no. 1, pp. 71–75, 1990. View at: Publisher Site | Google Scholar
  13. S. Agarwal and A. V. Rao, “Tomato lycopene and low density lipoprotein oxidation: a human dietary intervention study,” Lipids, vol. 33, no. 10, pp. 981–984, 1998. View at: Google Scholar
  14. C. Auger, P.-L. Teissedre, P. Gérain et al., “Dietary wine phenolics catechin, quercetin, and resveratrol efficiently protect hypercholesterolemic hamsters against aortic fatty streak accumulation,” Journal of Agricultural and Food Chemistry, vol. 53, no. 6, pp. 2015–2021, 2005. View at: Publisher Site | Google Scholar
  15. W. M. Loke, J. M. Proudfoot, J. M. Hodgson et al., “Specific dietary polyphenols attenuate atherosclerosis in apolipoprotein e-knockout mice by alleviating inflammation and endothelial dysfunction,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 4, pp. 749–757, 2010. View at: Publisher Site | Google Scholar
  16. M. Škerget, P. Kotnik, M. Hadolin, A. R. Hraš, M. Simonič, and Ž. Knez, “Phenols, proanthocyanidins, flavones and flavonols in some plant materials and their antioxidant activities,” Food Chemistry, vol. 89, no. 2, pp. 191–198, 2005. View at: Publisher Site | Google Scholar
  17. B. Sultana and F. Anwar, “Flavonols (kaempeferol, quercetin, myricetin) contents of selected fruits, vegetables and medicinal plants,” Food Chemistry, vol. 108, no. 3, pp. 879–884, 2008. View at: Publisher Site | Google Scholar
  18. D. M. Ribnicky, P. Kuhn, A. Poulev et al., “Improved absorption and bioactivity of active compounds from an anti-diabetic extract of Artemisia dracunculus L.,” International Journal of Pharmaceutics, vol. 370, no. 1-2, pp. 87–92, 2009. View at: Publisher Site | Google Scholar
  19. R. Patil, R. Patil, B. Ahirwar, and D. Ahirwar, “Isolation and characterization of anti-diabetic component (bioactivity-guided fractionation) from Ocimum sanctum L. (Lamiaceae) aerial part,” Asian Pacific Journal of Tropical Medicine, vol. 4, no. 4, pp. 278–282, 2011. View at: Publisher Site | Google Scholar
  20. J. Wainstein, T. Ganz, M. Boaz et al., “Olive leaf extract as a hypoglycemic agent in both human diabetic subjects and in rats,” Journal of Medicinal Food, vol. 15, no. 7, pp. 605–610, 2012. View at: Publisher Site | Google Scholar
  21. N. Tabassum and F. Ahmad, “Role of natural herbs in the treatment of hypertension,” Pharmacognosy Reviews, vol. 5, no. 9, pp. 30–40, 2011. View at: Publisher Site | Google Scholar
  22. S. I. Koo and S. K. Noh, “Green tea as inhibitor of the intestinal absorption of lipids: potential mechanism for its lipid-lowering effect,” Journal of Nutritional Biochemistry, vol. 18, no. 3, pp. 179–183, 2007. View at: Publisher Site | Google Scholar
  23. D. K. Singh, S. Banerjee, and T. D. Porter, “Green and black tea extracts inhibit HMG-CoA reductase and activate AMP kinase to decrease cholesterol synthesis in hepatoma cells,” The Journal of Nutritional Biochemistry, vol. 20, no. 10, pp. 816–822, 2009. View at: Publisher Site | Google Scholar
  24. M. Ismail, G. Al-Naqeep, and K. W. Chan, “Nigella sativa thymoquinone-rich fraction greatly improves plasma antioxidant capacity and expression of antioxidant genes in hypercholesterolemic rats,” Free Radical Biology and Medicine, vol. 48, no. 5, pp. 664–672, 2010. View at: Publisher Site | Google Scholar
  25. M. J. C. Rhodes and K. R. Price, “Analytical problems in the study of flavonoid compounds in onions,” Food Chemistry, vol. 57, no. 1, pp. 113–117, 1996. View at: Publisher Site | Google Scholar
  26. G. Dinelli, A. Bonetti, M. Minelli, I. Marotti, P. Catizone, and A. Mazzanti, “Content of flavonols in Italian bean (Phaseolus vulgaris L.) ecotypes,” Food Chemistry, vol. 99, no. 1, pp. 105–114, 2006. View at: Publisher Site | Google Scholar
  27. N. E. Rocha-Guzmán, A. Herzog, R. F. González-Laredo, F. J. Ibarra-Pérez, G. Zambrano-Galván, and J. A. Gallegos-Infante, “Antioxidant and antimutagenic activity of phenolic compounds in three different colour groups of common bean cultivars (Phaseolus vulgaris),” Food Chemistry, vol. 103, no. 2, pp. 521–527, 2007. View at: Publisher Site | Google Scholar
  28. B. Havsteen, “Flavonoids, a class of natural products of high pharmacological potency,” Biochemical Pharmacology, vol. 32, no. 7, pp. 1141–1148, 1983. View at: Publisher Site | Google Scholar
  29. M. G. L. Hertog, D. Kromhout, C. Aravanis et al., “Flavonoid intake and long-term risk of coronary heart disease and cancer in the Seven Countries Study,” Archives of Internal Medicine, vol. 155, no. 4, pp. 1184–1195, 1995. View at: Google Scholar
  30. D. D. Schramm and J. B. German, “Potential effects of flavonoids on the etiology of vascular disease,” The Journal of Nutritional Biochemistry, vol. 9, no. 10, pp. 560–566, 1998. View at: Publisher Site | Google Scholar
  31. M. Galleano, V. Calabro, P. D. Prince et al., “Flavonoids and metabolic syndrome,” Annals of the New York Academy of Sciences, vol. 1259, no. 1, pp. 87–94, 2012. View at: Publisher Site | Google Scholar
  32. J. A. Vinson, Y. A. Dabbagh, M. M. Serry, and J. Jang, “Plant flavonoids, especially tea flavonols, are powerful antioxidants using an in vitro oxidation model for heart disease,” Journal of Agricultural and Food Chemistry, vol. 43, no. 11, pp. 2800–2802, 1995. View at: Google Scholar
  33. P. C. H. Hollman, J. M. P. Van Trijp, M. N. C. P. Buysman et al., “Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man,” FEBS Letters, vol. 418, no. 1-2, pp. 152–156, 1997. View at: Publisher Site | Google Scholar
  34. C. Manach, A. Mazur, and A. Scalbert, “Polyphenols and prevention of cardiovascular diseases,” Current Opinion in Lipidology, vol. 16, no. 1, pp. 77–84, 2005. View at: Google Scholar
  35. R. Kleemann, L. Verschuren, M. Morrison et al., “Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models,” Atherosclerosis, vol. 218, no. 1, pp. 44–52, 2011. View at: Publisher Site | Google Scholar
  36. A. S. Koshy, L. Anila, and N. R. Vijayalakshmi, “Flavonoids from Garcinia cambogia lower lipid levels in hypercholesterolemic rats,” Food Chemistry, vol. 72, no. 3, pp. 289–294, 2001. View at: Publisher Site | Google Scholar
  37. L. Anila and N. R. Vijayalakshmi, “Antioxidant action of flavonoids from Mangifera indica and Emblica officinalis in hypercholesterolemic rats,” Food Chemistry, vol. 83, no. 4, pp. 569–574, 2003. View at: Publisher Site | Google Scholar
  38. Y. Zou, Y. Lu, and D. Wei, “Hypocholesterolemic effects of a flavonoid-rich extract of Hypericum perforatum L. in rats fed a cholesterol-rich diet,” Journal of Agricultural and Food Chemistry, vol. 53, no. 7, pp. 2462–2466, 2005. View at: Publisher Site | Google Scholar
  39. N. P. Visavadiya and A. V. R. L. Narasimhacharya, “Asparagus root regulates cholesterol metabolism and improves antioxidant status in hypercholesteremic rats,” Evidence-Based Complementary and Alternative Medicine, vol. 6, no. 2, pp. 219–226, 2009. View at: Publisher Site | Google Scholar
  40. J. Duarte, R. Pérez-Palencia, F. Vargas et al., “Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats,” British Journal of Pharmacology, vol. 133, no. 1, pp. 117–124, 2001. View at: Google Scholar
  41. M. F. Garciá-Saura, M. Galisteo, I. C. Villar et al., “Effects of chronic quercetin treatment in experimental renovascular hypertension,” Molecular and Cellular Biochemistry, vol. 270, no. 1-2, pp. 147–155, 2005. View at: Publisher Site | Google Scholar
  42. M. Sánchez, M. Galisteo, R. Vera et al., “Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats,” Journal of Hypertension, vol. 24, no. 1, pp. 75–84, 2006. View at: Google Scholar
  43. A. Abbass, “Efficiency of some antioxidants in reducing cardio-metabolic risks in obese rats,” Journal of American Science, vol. 7, pp. 1146–1159, 2011. View at: Google Scholar
  44. K.-H. Lee, E. Park, H.-J. Lee et al., “Effects of daily quercetin-rich supplementation on cardiometabolic risks in male smokers,” Nutrition Research and Practice, vol. 5, no. 1, pp. 28–33, 2011. View at: Publisher Site | Google Scholar
  45. L. K. Stewart, J. L. Soileau, D. Ribnicky et al., “Quercetin transiently increases energy expenditure but persistently decreases circulating markers of inflammation in C57BL/6J mice fed a high-fat diet,” Metabolism: Clinical and Experimental, vol. 57, no. 1, pp. S39–S46, 2008. View at: Publisher Site | Google Scholar
  46. E. Ohkoshi, H. Miyazaki, K. Shindo, H. Watanabe, A. Yoshida, and H. Yajima, “Constituents from the leaves of Nelumbo nucifera stimulate lipolysis in the white adipose tissue of mice,” Planta Medica, vol. 73, no. 12, pp. 1255–1259, 2007. View at: Publisher Site | Google Scholar
  47. M. Kobori, S. Masumoto, Y. Akimoto, and H. Oike, “Chronic dietary intake of quercetin alleviates hepatic fat accumulation associated with consumption of a Western-style diet in C57/BL6J mice,” Molecular Nutrition and Food Research, vol. 55, no. 4, pp. 530–540, 2011. View at: Publisher Site | Google Scholar
  48. B. Enkhmaa, K. Shiwaku, T. Katsube et al., “Mulberry (Morus alba L.) leaves and their major flavonol quercetin 3-(6-malonylglucoside) attenuate atherosclerotic lesion development in LDL receptor-deficient mice,” Journal of Nutrition, vol. 135, no. 4, pp. 729–734, 2005. View at: Google Scholar
  49. P. M. Ridker, “C-reactive protein: a simple test to help predict risk of heart attack and stroke,” Circulation, vol. 108, no. 12, pp. e81–e85, 2003. View at: Google Scholar
  50. S. Bhaskar, K. S. Kumar, K. Krishnan, and H. Antony, “Quercetin alleviates hypercholesterolemic diet induced inflammation during progression and regression of atherosclerosis in rabbits,” Nutrition, vol. 29, no. 1, pp. 219–229, 2013. View at: Publisher Site | Google Scholar
  51. S. Juźwiak, J. Wójcicki, K. Mokrzycki et al., “Effect of quercetin on experimental hyperlipidemia and atherosclerosis in rabbits,” Pharmacological Reports, vol. 57, no. 5, pp. 604–609, 2005. View at: Google Scholar
  52. S. Bhaskar, V. Shalini, and A. Helen, “Quercetin regulates oxidized LDL induced inflammatory changes in human PBMCs by modulating the TLR-NF-κB signaling pathway,” Immunobiology, vol. 216, no. 3, pp. 367–373, 2011. View at: Publisher Site | Google Scholar
  53. M. G. L. Hertog, P. C. H. Hollman, and B. Van de Putte, “Content of potentially anticareinogenic flavonoids of tea infusions, wines, and fruit juices,” Journal of Agricultural and Food Chemistry, vol. 41, no. 8, pp. 1242–1246, 1993. View at: Google Scholar
  54. K. H. Miean and S. Mohamed, “Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants,” Journal of Agricultural and Food Chemistry, vol. 49, no. 6, pp. 3106–3112, 2001. View at: Google Scholar
  55. P. Siddhuraju and K. Becker, “Antioxidant properties of various solvent extracts of total phenolic constituents from three different agroclimatic origins of drumstick tree (Moringa oleifera Lam.) leaves,” Journal of Agricultural and Food Chemistry, vol. 51, no. 8, pp. 2144–2155, 2003. View at: Publisher Site | Google Scholar
  56. M. Bajpai, A. Pande, S. K. Tewari, and D. Prakash, “Phenolic contents and antioxidant activity of some food and medicinal plants,” International Journal of Food Sciences and Nutrition, vol. 56, no. 4, pp. 287–291, 2005. View at: Publisher Site | Google Scholar
  57. F. Chimenti, F. Cottiglia, L. Bonsignore et al., “Quercetin as the active principle of Hypericum hircinum exerts a selective inhibitory activity against MAO-A: extraction, biological analysis, and computational study,” Journal of Natural Products, vol. 69, no. 6, pp. 945–949, 2006. View at: Publisher Site | Google Scholar
  58. B. Silva, P. J. Oliveira, A. Dias, and J. O. Malva, “Quercetin, kaempferol and biapigenin from hypericum perforatum are neuroprotective against excitotoxic insults,” Neurotoxicity Research, vol. 13, no. 3-4, pp. 265–279, 2008. View at: Publisher Site | Google Scholar
  59. P. Knekt, J. Kumpulainen, R. Järvinen et al., “Flavonoid intake and risk of chronic diseases,” American Journal of Clinical Nutrition, vol. 76, no. 3, pp. 560–568, 2002. View at: Google Scholar
  60. J. M. Calderon-Montano, E. Burgos-Morón, and M. López-Lázaro, “A review on the dietary flavonoid kaempferol,” Mini Review in Medicinal Chemistry, vol. 11, pp. 298–344, 2011. View at: Google Scholar
  61. Y. C. Xu, D. K. Y. Yeung, R. Y. K. Man, and S. W. S. Leung, “Kaempferol enhances endothelium-independent and dependent relaxation in the porcine coronary artery,” Molecular and Cellular Biochemistry, vol. 287, no. 1-2, pp. 61–67, 2006. View at: Publisher Site | Google Scholar
  62. H.-B. Xiao, X.-Y. Lu, X.-J. Chen, and Z.-L. Sun, “Protective effects of kaempferol against endothelial damage by an improvement in nitric oxide production and a decrease in asymmetric dimethylarginine level,” European Journal of Pharmacology, vol. 616, no. 1-3, pp. 213–222, 2009. View at: Publisher Site | Google Scholar
  63. R. Singh, B. Singh, S. Singh, N. Kumar, S. Kumar, and S. Arora, “Anti-free radical activities of kaempferol isolated from Acacia nilotica (L.) Willd. Ex. Del,” Toxicology in Vitro, vol. 22, no. 8, pp. 1965–1970, 2008. View at: Publisher Site | Google Scholar
  64. J. Kowalski, A. Samojedny, M. Paul, G. Pietsz, and T. Wilczok, “Effect of kaempferol on the production and gene expression of monocyte chemoattractant protein-1 in J774.2 macrophages,” Pharmacological Reports, vol. 57, no. 1, pp. 107–112, 2005. View at: Google Scholar
  65. L. Kong, C. Luo, X. Li, Y. Zhou, and H. He, “The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits,” Lipids in Health and Disease, vol. 12, no. 1, pp. 112–115, 2013. View at: Publisher Site | Google Scholar
  66. P. Chumark, P. Khunawat, Y. Sanvarinda et al., “The in vitro and ex vivo antioxidant properties, hypolipidaemic and antiatherosclerotic activities of water extract of Moringa oleifera Lam. leaves,” Journal of Ethnopharmacology, vol. 116, no. 3, pp. 439–446, 2008. View at: Publisher Site | Google Scholar
  67. M. G. Rajanandh, M. N. Satishkumar, K. Elango, and B. Suresh, “Moringa oleifera Lam. A herbal medicine for hyperlipidemia: a pre-clinical report,” Asian Pacific Journal of Tropical Disease, vol. 2, no. 2, pp. S790–S795, 2012. View at: Publisher Site | Google Scholar
  68. X.-K. Fang, J. Gao, and D.-N. Zhu, “Kaempferol and quercetin isolated from Euonymus alatus improve glucose uptake of 3T3-L1 cells without adipogenesis activity,” Life Sciences, vol. 82, no. 11-12, pp. 615–622, 2008. View at: Publisher Site | Google Scholar
  69. M. R. Sulaiman, Z. A. Zakaria, I. A. Daud, F. N. Ng, Y. C. Ng, and M. T. Hidayat, “Antinociceptive and anti-inflammatory activities of the aqueous extract of Kaempferia galanga leaves in animal models,” Journal of Natural Medicines, vol. 62, no. 2, pp. 221–227, 2008. View at: Publisher Site | Google Scholar
  70. J. M. Harnly, R. F. Doherty, G. R. Beecher et al., “Flavonoid content of U.S. fruits, vegetables, and nuts,” Journal of Agricultural and Food Chemistry, vol. 54, no. 26, pp. 9966–9977, 2006. View at: Publisher Site | Google Scholar
  71. A. M. Gray and P. R. Flatt, “Nature's own pharmacy: the diabetes perspective,” Proceedings of the Nutrition Society, vol. 56, no. 1999, pp. 507–517, 1997. View at: Google Scholar
  72. L. Mira, M. T. Fernandez, M. Santos, R. Rocha, M. H. Florêncio, and K. R. Jennings, “Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity,” Free Radical Research, vol. 36, no. 11, pp. 1199–1208, 2002. View at: Publisher Site | Google Scholar
  73. T. P. T. Cushnie and A. J. Lamb, “Antimicrobial activity of flavonoids,” International Journal of Antimicrobial Agents, vol. 26, no. 5, pp. 343–356, 2005. View at: Publisher Site | Google Scholar
  74. Y. Shimmyo, T. Kihara, A. Akaike, T. Niidome, and H. Sugimoto, “Three distinct neuroprotective functions of myricetin against glutamate-induced neuronal cell death: involvement of direct inhibition of caspase-3,” Journal of Neuroscience Research, vol. 86, no. 8, pp. 1836–1845, 2008. View at: Publisher Site | Google Scholar
  75. N. J. Kang, S. K. Jung, K. W. Lee, and H. J. Lee, “Myricetin is a potent chemopreventive phytochemical in skin carcinogenesis,” Annals of the New York Academy of Sciences, vol. 1229, no. 1, pp. 124–132, 2011. View at: Publisher Site | Google Scholar
  76. Y. Li and Y. Ding, “Minireview: therapeutic potential of myricetin in diabetes mellitus,” Food Science and Human Wellness, vol. 1, pp. 19–25, 2012. View at: Google Scholar
  77. S. Godse, M. Mohan, V. Kasture, and S. Kasture, “Effect of myricetin on blood pressure and metabolic alterations in fructose hypertensive rats,” Pharmaceutical Biology, vol. 48, no. 5, pp. 494–498, 2010. View at: Publisher Site | Google Scholar
  78. C. J. Chang, T.-F. Tzeng, S.-S. Liou, Y.-S. Chang, and I.-M. Liu, “Myricetin increases hepatic peroxisome proliferator-activated receptor protein expression and decreases plasma lipids and adiposity in rats,” Evidence-Based Complementary and Alternative Medicine, vol. 2012, Article ID 787152, 11 pages, 2012. View at: Publisher Site | Google Scholar
  79. D. T. Ha, P. T. Thuang, and N. D. Thuan, “Protective action of Ampelopsis cantoniensis and its major constituent—myricetin against LDL oxidation,” Journal of Chemistry, vol. 45, pp. 768–771, 2007. View at: Google Scholar
  80. T.-W. Lian, L. Wang, Y.-H. Lo, I.-J. Huang, and M.-J. Wu, “Fisetin, morin and myricetin attenuate CD36 expression and oxLDL uptake in U937-derived macrophages,” Biochimica et Biophysica Acta: Molecular and Cell Biology of Lipids, vol. 1781, no. 10, pp. 601–609, 2008. View at: Publisher Site | Google Scholar
  81. B. D. Paul, G. S. Rao, and G. J. Kapadia, “Isolation of myricadiol, myricitrin, taraxerol, and taraxerone from Myrica cerifera L. root bark,” Journal of Pharmaceutical Sciences, vol. 63, no. 6, pp. 958–959, 1974. View at: Google Scholar
  82. W. L. R. Barbosa, A. Peres, S. Gallori et al., “Determination of myricetin derivatives in Chrysobalanus icaco L., (Chrysobalanaceae),” Brazilian Journal of Pharmacognosy, vol. 16, pp. 333–337, 2006. View at: Google Scholar
  83. S. Kreft, M. Knapp, and I. Kreft, “Extraction of rutin from buckwheat (Fagopyrum esculentum moench) seeds and determination by capillary electrophoresis,” Journal of Agricultural and Food Chemistry, vol. 47, no. 11, pp. 4649–4652, 1999. View at: Publisher Site | Google Scholar
  84. D. Metodiewa, A. Kochman, and S. Karolczak, “Evidence for antiradical and antioxidant properties of four biologically active N,N-diethylamioethyl ethers of flavanone oximes: a comparison with natural polyphenolic flavonoid (rutin) action,” International Union of Biochemistry and Molecular Life, vol. 41, no. 5, pp. 1067–1075, 1997. View at: Google Scholar
  85. S. A. Aherne and N. M. O'Brien, “Protection by the flavonoids myricetin, quercetin, and rutin against hydrogen peroxide-induced DNA damage in Caco-2 and Hep G2 cells,” Nutrition and Cancer, vol. 34, no. 2, pp. 160–166, 1999. View at: Google Scholar
  86. T. Guardia, A. E. Rotelli, A. O. Juarez, and L. E. Pelzer, “Anti-inflammatory properties of plant flavonoids. Effects of rutin, quercetin and hesperidin on adjuvant arthritis in rat,” Farmaco, vol. 56, no. 9, pp. 683–687, 2001. View at: Publisher Site | Google Scholar
  87. H. J. Chan, Y. L. Ji, H. C. Chul, and J. K. Chang, “Anti-asthmatic action of quercetin and rutin in conscious guinea-pigs challenged with aerosolized ovalbumin,” Archives of Pharmacal Research, vol. 30, no. 12, pp. 1599–1607, 2007. View at: Google Scholar
  88. G. B. Reddy, P. Muthenna, C. Akileshwari, M. Saraswat, and J. M. Petrash, “Inhibition of aldose reductase and sorbitol accumulation by dietary rutin,” Current Science, vol. 101, no. 9, pp. 1191–1197, 2011. View at: Google Scholar
  89. W. K. Dae, K. H. In, S. L. Soon et al., “Germinated buckwheat extract decreases blood pressure and nitrotyrosine immunoreactivity in aortic endothelial cells in spontaneously hypertensive rats,” Phytotherapy Research, vol. 23, no. 7, pp. 993–998, 2009. View at: Publisher Site | Google Scholar
  90. C.-L. Hsu, C.-H. Wu, S.-L. Huang, and G.-C. Yen, “Phenolic compounds rutin and o-coumaric acid ameliorate obesity induced by high-fat diet in rats,” Journal of Agricultural and Food Chemistry, vol. 57, no. 2, pp. 425–431, 2009. View at: Publisher Site | Google Scholar
  91. O. N. Voskresensky and V. N. Bobyrev, “Effect of ascorbic acid and rutin on the development of experimental peroxide atherosclerosis,” Farmakologiyai Toksikologiya, vol. 42, no. 4, pp. 378–382, 1979. View at: Google Scholar
  92. K. F. R. Santos, T. T. Oliveira, T. J. Nagem, A. S. Pinto, and M. G. A. Oliveira, “Hypolipidaemic effects of naringenin, rutin, nicotinic acid and their associations,” Pharmacological Research, vol. 40, no. 6, pp. 493–496, 1999. View at: Publisher Site | Google Scholar
  93. A. Kanashiro, D. C. O. andrade, L. M. Kabeya et al., “Modulatory effects of rutin on biochemical and hematological parameters in hypercholesterolemic Golden Syrian hamsters,” Annals of the Brazilian Academy of Sciences, vol. 81, no. 1, pp. 67–71, 2009. View at: Google Scholar
  94. B. Buszewski, S. Kawka, Z. Suprynowicz, and T. Wolski, “Simultaneous isolation of Rutin and Esculin from plant material and drugs using solid-phase extraction,” Journal of Pharmaceutical and Biomedical Analysis, vol. 11, no. 3, pp. 211–215, 1993. View at: Publisher Site | Google Scholar
  95. D. J. Afshar and A. Delazar, “Rutin from Ruta graveolens L.,” DARU Journal of Pharmaceutical Sciences, vol. 4, pp. 1–12, 1994. View at: Google Scholar
  96. M. Atanassova and V. Bagdassarian, “Rutin in plant products,” Journal of the University of Chemical Technology and Metallurgy, vol. 44, pp. 201–203, 2009. View at: Google Scholar
  97. P. Shukla, B. Gopalkrishna, and P. Shukla, “Isolation of rutin from Phyllanthus amarus,” International Journal of Pharmaceutical Sciences and Research, vol. 3, pp. 1198–1201, 2012. View at: Google Scholar
  98. S.-M. Jeon, S.-H. Bok, M.-K. Jang et al., “Comparison of antioxidant effects of naringin and probucol in cholesterol-fed rabbits,” Clinica Chimica Acta, vol. 317, no. 1-2, pp. 181–190, 2002. View at: Publisher Site | Google Scholar
  99. F. A. A. Van Acker, O. Schouten, G. R. M. M. Haenen, W. J. F. Van Der Vijgh, and A. Bast, “Flavonoids can replace α-tocopherol as an antioxidant,” FEBS Letters, vol. 473, no. 2, pp. 145–148, 2000. View at: Publisher Site | Google Scholar
  100. N. M. Borradaile, K. K. Carroll, and E. M. Kurowska, “Regulation of HepG2 cell apolipoprotein B metabolism by the citrus flavanones hesperetin and naringenin,” Lipids, vol. 34, no. 6, pp. 591–598, 1999. View at: Publisher Site | Google Scholar
  101. S.-H. Lee, T.-S. Jeong, Y. B. Park, Y.-K. Kwon, M.-S. Choi, and S.-H. Bok, “Hypocholesterolemic effect of hesperetin mediated by inhibition of 3- hydroxy-3-methylgultaryl coenzyme A reductase and acyl coenzyme A: cholesterol acyltransferase in rats fed high-cholesterol diet,” Nutrition Research, vol. 19, no. 8, pp. 1245–1258, 1999. View at: Publisher Site | Google Scholar
  102. S. H. Lee, Y. B. Park, K. H. Bae et al., “Cholesterol-lowering activity of naringenin via inhibition of 8-hydroxy-3-methylglutaryl coenzyme a reductase and acyl coenzyme A: cholesterol acyltransferase in rats,” Annals of Nutrition and Metabolism, vol. 43, no. 3, pp. 173–180, 1999. View at: Publisher Site | Google Scholar
  103. E. M. Kurowska, N. M. Borradaile, J. D. Spence, and K. K. Carroll, “Hypocholesterolemic effects of dietary citrus juices in rabbits,” Nutrition Research, vol. 20, no. 1, pp. 121–129, 2000. View at: Publisher Site | Google Scholar
  104. E. M. Kurowska, J. D. Spence, J. Jordan et al., “HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia,” American Journal of Clinical Nutrition, vol. 72, no. 5, pp. 1095–1100, 2000. View at: Google Scholar
  105. J.-J. Lee, H. Yi, I.-S. Kim et al., “(2S)-Naringenin from Typha angustata inhibits vascular smooth muscle cell proliferation via a G0/G1 arrest,” Journal of Ethnopharmacology, vol. 139, pp. 873–878, 2012. View at: Google Scholar
  106. E. E. Mulvihill, J. M. Assini, B. G. Sutherland et al., “Naringenin decreases progression of atherosclerosis by improving dyslipidemia in high-fat-fed low-density lipoprotein receptor-null mice,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, no. 4, pp. 742–748, 2010. View at: Publisher Site | Google Scholar
  107. M. F. Ruh, T. Zacharewski, K. Connor, J. Howell, I. Chen, and S. Safe, “Naringenin: a weakly estrogenic bioflavonoid that exhibits antiestrogenic activity,” Biochemical Pharmacology, vol. 50, no. 9, pp. 1485–1493, 1995. View at: Publisher Site | Google Scholar
  108. G. G. J. M. Kuiper, J. G. Lemmen, B. Carlsson et al., “Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor β,” Endocrinology, vol. 139, no. 10, pp. 4252–4263, 1998. View at: Google Scholar
  109. R. S. Rosenberg, L. Grass, D. J. A. Jenkins, C. W. C. Kendall, and E. P. Diamandis, “Modulation of androgen and progesterone receptors by phytochemicals in breast cancer cell lines,” Biochemical and Biophysical Research Communications, vol. 248, no. 3, pp. 935–939, 1998. View at: Publisher Site | Google Scholar
  110. H. Déchaud, C. Ravard, F. Claustrat, A. B. De La Perrière, and M. Pugeat, “Xenoestrogen interaction with human sex hormone-binding globulin (hSHBG),” Steroids, vol. 64, no. 5, pp. 328–334, 1999. View at: Publisher Site | Google Scholar
  111. J. A. Manthey, N. Guthrie, and K. Grohmann, “Biological properties of citrus flavonoids pertaining to cancer and inflammation,” Current Medicinal Chemistry, vol. 8, no. 2, pp. 135–153, 2001. View at: Google Scholar
  112. K. Yoon, L. Pallaroni, M. Stoner, K. Gaido, and S. Safe, “Differential activation of wild-type and variant forms of estrogen receptor α by synthetic and natural estrogenic compounds using a promoter containing three estrogen-responsive elements,” Journal of Steroid Biochemistry and Molecular Biology, vol. 78, no. 1, pp. 25–32, 2001. View at: Publisher Site | Google Scholar
  113. M. Krause and R. Galensa, “Determination of naringenin and naringenin-chalcone in tomato skins by reversed phase HPLC after solid phase extraction,” Zeitschrift für Lebensmittel-Untersuchung und -Forschung, vol. 194, no. 1, pp. 29–32, 1992. View at: Publisher Site | Google Scholar
  114. S. Kawaii, Y. Tomono, E. Katase, K. Ogawa, and M. Yano, “Quantitation of flavonoid constituents in Citrus fruits,” Journal of Agricultural and Food Chemistry, vol. 47, no. 9, pp. 3565–3571, 1999. View at: Publisher Site | Google Scholar
  115. H. T. Olsen, G. I. Stafford, J. van Staden, S. B. Christensen, and A. K. Jäger, “Isolation of the MAO-inhibitor naringenin from Mentha aquatica L.,” Journal of Ethnopharmacology, vol. 117, no. 3, pp. 500–502, 2008. View at: Publisher Site | Google Scholar
  116. L. Liu, S. Shan, K. Zhang, Z.-Q. Ning, X.-P. Lu, and Y.-Y. Cheng, “Naringenin and hesperetin, two flavonoids derived from Citrus aurantium up-regulate transcription of adiponectin,” Phytotherapy Research, vol. 22, no. 10, pp. 1400–1403, 2008. View at: Publisher Site | Google Scholar
  117. C. A. de Andrade, J. L. D. S. Carvalho, M. M. Cunico et al., “Antioxidant and antibacterial activity of extracts, fractions and isolated substances from the flowers of Acacia podalyriifolia A. Cunn. ex G. Don,” Brazilian Journal of Pharmaceutical Sciences, vol. 46, no. 4, pp. 715–721, 2010. View at: Google Scholar
  118. K. Yoshino, Y. Hara, M. Sano, and I. Tomita, “Antioxidative effects of black tea theaflavins and thearubigin on lipid peroxidation of liver homogenates induced by tert-butyl hydroperoxide,” Biological and Pharmaceutical Bulletin, vol. 17, no. 1, pp. 146–149, 1994. View at: Google Scholar
  119. N. Salah, N. J. Miller, G. Paganga, L. Tijburg, G. P. Bolwell, and C. Rice-Evans, “Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain-breaking antioxidants,” Archives of Biochemistry and Biophysics, vol. 322, no. 2, pp. 339–346, 1995. View at: Publisher Site | Google Scholar
  120. K. F. Gey, “Ten-year retrospective on the antioxidant hypothesis of arteriosclerosis: threshold plasma levels of antioxidant micronutrients related to minimum cardiovascular risk,” Journal of Nutritional Biochemistry, vol. 6, no. 4, pp. 206–236, 1995. View at: Publisher Site | Google Scholar
  121. J. A. Vita, “Tea consumption and cardiovascular disease: effects on endothelial function,” Journal of Nutrition, vol. 133, no. 10, pp. 3293s–3297s, 2003. View at: Google Scholar
  122. V. Stangl, M. Lorenz, and K. Stangl, “The role of tea and tea flavonoids in cardiovascular health,” Molecular Nutrition and Food Research, vol. 50, no. 2, pp. 218–228, 2006. View at: Publisher Site | Google Scholar
  123. V. Stangl, H. Dreger, K. Stangl, and M. Lorenz, “Molecular targets of tea polyphenols in the cardiovascular system,” Cardiovascular Research, vol. 73, no. 2, pp. 348–358, 2007. View at: Publisher Site | Google Scholar
  124. S. M. Shenouda and J. A. Vita, “Effects of flavonoid-containing beverages and EGCG on endothelial function,” Journal of the American College of Nutrition, vol. 26, no. 4, pp. 366s–372s, 2007. View at: Google Scholar
  125. N. Khan and H. Mukhtar, “Tea polyphenols for health promotion,” Life Sciences, vol. 81, no. 7, pp. 519–533, 2007. View at: Publisher Site | Google Scholar
  126. H. Y. Ahn, Y. Xu, and S. T. Davidge, “Epigallocatechin-3-O-gallate inhibits TNFα-induced monocyte chemotactic protein-1 production from vascular endothelial cells,” Life Sciences, vol. 82, no. 17-18, pp. 964–968, 2008. View at: Publisher Site | Google Scholar
  127. T. Furuyashiki, H. Nagayasu, Y. Aoki et al., “Tea catechin suppresses adipocyte differentiation accompanied by down-regulation of PPARγ2 and C/EBPα in 3T3-L1 cells,” Bioscience, Biotechnology and Biochemistry, vol. 68, no. 11, pp. 2353–2359, 2004. View at: Publisher Site | Google Scholar
  128. M. A. Potenza, F. L. Marasciulo, M. Tarquinio et al., “EGCG, a green tea polyphenol, improves endothelial function and insulin sensitivity, reduces blood pressure, and protects against myocardial I/R injury in SHR,” American Journal of Physiology: Endocrinology and Metabolism, vol. 292, no. 5, pp. E1378–E1387, 2007. View at: Publisher Site | Google Scholar
  129. C. A. Bursill and P. D. Roach, “A green tea catechin extract upregulates the hepatic low-density lipoprotein receptor in rats,” Lipids, vol. 42, no. 7, pp. 621–627, 2007. View at: Publisher Site | Google Scholar
  130. M. E. Widlansky, N. M. Hamburg, E. Anter et al., “Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease,” Journal of the American College of Nutrition, vol. 26, no. 2, pp. 95–102, 2007. View at: Google Scholar
  131. V. Ossipov, K. Nurmi, J. Loponen, E. Haukioja, and K. Pihlaja, “High-performance liquid chromatographic separation and identification of phenolic compounds from leaves of Betula pubescens and Betula pendula,” Journal of Chromatography A, vol. 721, no. 1, pp. 59–68, 1996. View at: Publisher Site | Google Scholar
  132. C. Kirszberg, D. Esquenazi, C. S. Alviano, and V. M. Rumjanek, “The effect of a catechin-rich extract of Cocos nucifera on lymphocytes proliferation,” Phytotherapy Research, vol. 17, no. 9, pp. 1054–1058, 2003. View at: Publisher Site | Google Scholar
  133. Z. Charrouf and D. Guillaume, “Phenols and polyphenols from Argania spinosa,” American Journal of Food Technology, vol. 2, no. 7, pp. 679–683, 2007. View at: Google Scholar
  134. P. Daisy, K. Balasubramanian, M. Rajalakshmi, J. Eliza, and J. Selvaraj, “Insulin mimetic impact of Catechin isolated from Cassia fistula on the glucose oxidation and molecular mechanisms of glucose uptake on Streptozotocin-induced diabetic Wistar rats,” Phytomedicine, vol. 17, no. 1, pp. 28–36, 2010. View at: Publisher Site | Google Scholar
  135. Y. Arai, S. Watanabe, M. Kimira, K. Shimoi, R. Mochizuki, and N. Kinae, “Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration,” Journal of Nutrition, vol. 130, no. 9, pp. 2243–2250, 2000. View at: Google Scholar
  136. R. P. Constantin, J. Constantin, C. L. S. Pagadigorria et al., “Prooxidant activity of fisetin: effects on energy metabolism in the rat liver,” Journal of Biochemical and Molecular Toxicology, vol. 25, no. 2, pp. 117–126, 2011. View at: Publisher Site | Google Scholar
  137. F. Y. Goh, N. Upton, S. Guan et al., “Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF-κB,” European Journal of Pharmacology, vol. 679, no. 1-3, pp. 109–116, 2012. View at: Publisher Site | Google Scholar
  138. P.-M. Yang, H.-H. Tseng, C.-W. Peng, W.-S. Chen, and S.-J. Chiu, “Dietary flavonoid fisetin targets caspase-3-deficient human breast cancer MCF-7 cells by induction of caspase-7-associated apoptosis and inhibition of autophagy,” International Journal of Oncology, vol. 40, no. 2, pp. 469–478, 2012. View at: Publisher Site | Google Scholar
  139. N. Khan, F. Afaq, D. N. Syed, and H. Mukhtar, “Fisetin, a novel dietary flavonoid, causes apoptosis and cell cycle arrest in human prostate cancer LNCaP cells,” Carcinogenesis, vol. 29, no. 5, pp. 1049–1056, 2008. View at: Publisher Site | Google Scholar
  140. G. S. Prasath and S. P. Subramanian, “Modulatory effects of fisetin, a bioflavonoid, on hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in hepatic and renal tissues in streptozotocin-induced diabetic rats,” European Journal of Pharmacology, vol. 668, no. 3, pp. 492–496, 2011. View at: Publisher Site | Google Scholar
  141. Y. Lee and E. J. Bae, “Inhibition of mitotic clonal expansion mediates fisetin-exerted prevention of adipocyte differentiation in 3T3-L1 cells,” Archives of Pharmacal Research, vol. 36, pp. 1377–1384, 2013. View at: Publisher Site | Google Scholar
  142. C. H. Jung, H. Kim, J. Ahn, T.-I. Jeon, D.-H. Lee, and T.-Y. Ha, “Fisetin regulates obesity by targeting mTORC1 signaling,” The Journal of Nutritional Biochemistry, vol. 24, no. 8, pp. 1547–1554, 2013. View at: Publisher Site | Google Scholar
  143. J. Reed, “Cranberry flavonoids, atherosclerosis and cardiovascular health,” Critical Reviews in Food Science and Nutrition, vol. 42, no. 3, pp. 301–316, 2002. View at: Google Scholar
  144. D. Steinberg, S. Parthasarathy, T. E. Carew, J. C. Khoo, and J. L. Witztum, “Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity,” The New England Journal of Medicine, vol. 320, no. 14, pp. 915–924, 1989. View at: Google Scholar
  145. C. V. De Whalley, S. M. Rankin, J. R. S. Hoult, W. Jessup, and D. S. Leake, “Flavonoids inhibit the oxidative modification of low density lipoproteins by macrophages,” Biochemical Pharmacology, vol. 39, no. 11, pp. 1743–1750, 1990. View at: Publisher Site | Google Scholar
  146. M. Gábor and E. Eperjessy, “Antibacterial effect of fisetin and fisetinidin,” Nature, vol. 212, no. 5067, p. 1273, 1966. View at: Publisher Site | Google Scholar
  147. J. Lako, V. C. Trenerry, M. Wahlqvist, N. Wattanapenpaiboon, S. Sotheeswaran, and R. Premier, “Phytochemical flavonols, carotenoids and the antioxidant properties of a wide selection of Fijian fruit, vegetables and other readily available foods,” Food Chemistry, vol. 101, no. 4, pp. 1727–1741, 2007. View at: Publisher Site | Google Scholar
  148. J.-D. Lee, J.-E. Huh, G. Jeon et al., “Flavonol-rich RVHxR from Rhus verniciflua stokes and its major compound fisetin inhibits inflammation-related cytokines and angiogenic factor in rheumatoid arthritic fibroblast-like synovial cells and in vivo models,” International Immunopharmacology, vol. 9, no. 3, pp. 268–276, 2009. View at: Publisher Site | Google Scholar
  149. T. D. A. Forbes and B. A. Clement, “Chemistry of Acacia's from South Texas,” Texas A&M Agricultural Research and Extension Center, pp. 4–14, 2010. View at: Google Scholar
  150. H.-H. Lin, J.-H. Chen, and C.-J. Wang, “Chemopreventive properties and molecular mechanisms of the bioactive compounds in Hibiscus sabdariffa linne,” Current Medicinal Chemistry, vol. 18, no. 8, pp. 1245–1254, 2011. View at: Publisher Site | Google Scholar
  151. J. H. Chen, C. W. Tsai, C. P. Wang, and H. H. Lin, “Anti-atherosclerotic potential of gossypetin via inhibiting LDL oxidation and foam cell formation,” Toxicology and Applied Pharmacology, vol. 272, pp. 313–324, 2013. View at: Google Scholar
  152. J. B. Harborne, “Gossypetin and herbacetin as taxonomic markers in higher plants,” Phytochemistry, vol. 8, no. 1, pp. 177–183, 1969. View at: Google Scholar
  153. G. Bendz, Chemistry in Botanical Classification: Medicine and Natural Sciences, Science, 2013.
  154. S. M. Rankin, C. V. De Whalley, J. R. S. Hoult et al., “The modification of low density lipoprotein by the flavonoids myricetin and gossypetin,” Biochemical Pharmacology, vol. 45, no. 1, pp. 67–75, 1993. View at: Publisher Site | Google Scholar
  155. H. Mozaffari-Khosravi, B.-A. Jalali-Khanabadi, M. Afkhami-Ardekani, F. Fatehi, and M. Noori-Shadkam, “The effects of sour tea (Hibiscus sabdariffa) on hypertension in patients with type II diabetes,” Journal of Human Hypertension, vol. 23, no. 1, pp. 48–54, 2009. View at: Publisher Site | Google Scholar
  156. E. V. Villalpando-Arteaga, E. Mendieta-Condado, H. Esquivel-Solís et al., “Hibiscus sabdariffa L. aqueous extract attenuates hepatic steatosis through down-regulation of PPAR-γ and SREBP-1c in diet-induced obese mice,” Food & Function, vol. 4, pp. 618–626, 2013. View at: Google Scholar

Copyright © 2014 Shamala Salvamani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

More related articles

 PDF Download Citation Citation
 Download other formatsMore
 Order printed copiesOrder

Related articles

We are committed to sharing findings related to COVID-19 as quickly as possible. We will be providing unlimited waivers of publication charges for accepted research articles as well as case reports and case series related to COVID-19. Review articles are excluded from this waiver policy. Sign up here as a reviewer to help fast-track new submissions.